5-16670764-G-A

Variant names:

• chr5-16670764-G-A
• rs532130077
• NM_012334.3:c.5645C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012334.3(MYO10):​c.5645C>T​(p.Thr1882Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1882K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: MYO10 NM_012334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.45
• Publications: 0 publications found

Genes affected

MYO10 (HGNC:7593): (myosin X) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-10 (MYH10). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. This gene functions as an actin-based molecular motor and plays a role in integration of F-actin and microtubule cytoskeletons during meiosis. [provided by RefSeq, Dec 2011]

RETREG1-AS1 (HGNC:55551): (RETREG1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31634274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO10	NM_012334.3	MANE Select	c.5645C>T	p.Thr1882Met	missense	Exon 39 of 41	NP_036466.2	Q9HD67-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO10	ENST00000513610.6	TSL:1 MANE Select	c.5645C>T	p.Thr1882Met	missense	Exon 39 of 41	ENSP00000421280.1	Q9HD67-1
	MYO10	ENST00000274203.13	TSL:5	c.5678C>T	p.Thr1893Met	missense	Exon 39 of 41	ENSP00000274203.10	A0A0A0MQX1
	MYO10	ENST00000505695.5	TSL:2	c.3662C>T	p.Thr1221Met	missense	Exon 21 of 23	ENSP00000421170.1	E9PEW5

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 249154 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461710 Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000331 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.5	L
PhyloP100		6.4
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.046	D
Polyphen		0.96	D
Vest4		0.63
MutPred		0.34		Loss of phosphorylation at T1882 (P = 0.0143)
MVP		0.92
MPC		0.51
ClinPred		0.55	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.31
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs532130077; hg19: chr5-16670873;